tbuckley/cabot-search huggingface dataset:
Localizing Post-Admixture Adaptive Variants with Object Detection on Ancestry-Painted Chromosomes
Authors: Iman Hamid, Katharine L Korunes, Daniel R Schrider, Amy Goldberg
Journal: Molecular Biology and Evolution (2023)

Abstract Gene flow between previously differentiated populations during the founding of an admixed or hybrid population has the potential to introduce adaptive alleles into the new population. If the adaptive allele is common in one source population, but not the other, then as the adaptive allele rises in frequency in the admixed population, genetic ancestry from the source containing the adaptive allele will increase nearby as well. Patterns of genetic ancestry have therefore been used to identify post-admixture positive selection in humans and other animals, including examples in immunity, metabolism, and animal coloration. A common method identifies regions of the genome that have local ancestry “outliers” compared with the distribution across the rest of the genome, considering each locus independently. However, we lack theoretical models for expected distributions of ancestry under various demographic scenarios, resulting in potential false positives and false negatives. Further, ancestry patterns between distant sites are often not independent. As a result, current methods tend to infer wide genomic regions containing many genes as under selection, limiting biological interpretation. Instead, we develop a deep learning object detection method applied to images generated from local ancestry-painted genomes. This approach preserves information from the surrounding genomic context and avoids potential pitfalls of user-defined summary statistics. We find the method is robust to a variety of demographic misspecifications using simulated data. Applied to human genotype data from Cabo Verde, we localize a known adaptive locus to a single narrow region compared with multiple or long windows obtained using two other ancestry-based methods.
<i>JAMA Psychiatry</i>—The Year in Review, 2022
Authors: Dost Öngür
Journal: JAMA Psychiatry (2023)

The past year saw ongoing impacts from the COVID-19 pandemic as well as new hope for recovery in the world and in our field.At JAMA Psychiatry, we worked hard to set and maintain the highest standards despite ongoing challenges.We published studies on psilocybin-assisted psychotherapy for alcohol use disorder, 1 association of baseline psychopathology with post-COVID-19 conditions, 2 increase in drug overdose mortality rates during the pandemic, 3 and many others on important topics running the gamut from clinical trials and epidemiology to clinical neuroscience and genetics.In 2022, the journal received 1763 submissions of which 1441 were research manuscripts (Table ).We had an acceptance rate of 9% of all submitted research manuscripts.As we do every year, we strived to provide authors with rapid decisions: the median turnaround time for manuscripts rejected without peer review was 3 days, and the median time from receipt to first decision for peer-reviewed manuscripts was 34 days.I want to acknowledge, as I do every year, the excellent contributions made by the journal's expert peer reviewers.The complete list of peer reviewers for the journal in the past year can be found in "JAMA Psychiatry Peer Reviewers in 2022." 7he journal's metrics on several other fronts remained robust in the past year, and JAMA Psychiatry continues as a highly influential journal.In 2022, the journal's impact factor was 25.94, continuing its upward trend with an increase of over 4 points compared with 2021.We had over 81 000 followers on social media, and more than 6.9 million article views and downloads.2][3][4][5][6] Also in 2022, we successfully launched the Brief Reports article type in the journal.Brief Reports can communicate innovative and disruptive research findings, which may not be appropriate for a full-length Original Investigation but still require more space than available in the Research Letter format.Every journal has an identity, and we want JAMA Psychiatry to be known for publishing some of the best original research in psychiatry.We do have sections for shorter Viewpoints, Editorials, Neuroscience and Psychiatry articles, and others, but full-length data research articles constitute the lifeblood of the journal.We seek original research on a diverse range of topics in the field written by diverse groups of authors.This mission makes JAMA Psychiatry highly sensitive to potential tensions between pursuing high-impact and attention-getting articles with novel findings on the one hand and ensuring that articles we publish will stand the test of time on the other.As a result of this sensitivity, our team follows debates around rigor in scientific research closely.In 2022, several topics caught our attention: one was concerns regard-Table.
Expanding the Donor Pool for Organ Transplant Using Organs From Donors With Cancer
Authors: Yuman Fong
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials
Authors: Bei Pan, Long Ge, Honghao Lai, Liangying Hou, Chen Tian, Qi Wang, Kelu Yang, Yao Lu, Hongfei Zhu, Mengting Li, Deren Wang, Xiuxia Li, Yuqing Zhang, Ya Gao, Ming Liu, Guowu Ding, Jinhui Tian, Kehu Yang
Journal: Drugs (2023)
Prevalence of Myopia in Children Before, During, and After COVID-19 Restrictions in Hong Kong
Authors: Xiu Juan Zhang, Yuzhou Zhang, Ka Wai Kam, Fangyao Tang, Yi Li, Mandy P. H. Ng, Alvin L. Young, Patrick Ip, Clement C. Tham, Li Jia Chen, Chi Pui Pang, Jason C. Yam
Journal: JAMA Network Open (2023)

Importance Childhood myopia increased during the COVID-19 pandemic. Limited evidence exists about whether myopia development was reversed or worsened after the lockdown. Objective To determine the prevalence of myopia and its associated factors before, during, and after COVID-19 restrictions. Design, Setting, and Participants This population-based, repeated cross-sectional study evaluated children aged 6 to 8 years from the Hong Kong Children Eye Study between 2015 and 2021 in 3 cohorts: before COVID-19 (2015-2019), during COVID-19 restrictions (2020), and after COVID-19 restrictions were lifted (2021). Exposures All the children received ocular examinations, including cycloplegic autorefraction and axial length. Data about the children’s lifestyle, including time spent outdoors, near-work time, and screen time, were collected from a standardized questionnaire. Main Outcomes and Measures The main outcomes were the prevalence of myopia, mean spherical equivalent refraction, axial length, changes in lifestyle, and the associated factors over 7 years. Data were analyzed using descriptive statistics, logistic regression, and generalized estimating equations. Results Of 20 527 children (mean [SD] age, 7.33 [0.89] years; 52.8% boys and 47.2% girls), myopia prevalence was stable from 2015 to 2019 (23.5%-24.9%; P = .90) but increased to 28.8% ( P &amp;amp;lt; .001) in 2020 and 36.2% ( P &amp;amp;lt; .001) in 2021. The mean (SD) time spent outdoors was much lower in 2020 (0.85 [0.53] h/d; P &amp;amp;lt; .001) and 2021 (1.26 [0.48] h/d; P &amp;amp;lt; .001) compared with pre–COVID-19 levels (1.40 [0.47]-1.46 [0.65] h/d). The trend was reversed for total near-work time and screen time. High myopia prevalence was associated with the COVID-19 pandemic (odds ratio [OR], 1.40; 95% CI, 1.28-1.54; P &amp;amp;lt; .001), younger age (OR, 1.84; 95% CI, 1.76-1.93; P &amp;amp;lt; .001), male sex (OR, 1.11; 95% CI, 1.03-1.21; P = .007), lower family income (OR, 1.05; 95% CI, 1.00-1.09; P = .04), and parental myopia (OR, 1.61; 95% CI, 1.52-1.70; P &amp;amp;lt; .001). During the pandemic, mean (SD) near-work and screen times in children from lower-income families were 5.16 (2.05) h/d and 3.44 (1.97) h/d, more than from higher-income families (4.83 [1.85] and 2.90 [1.61] h/d, respectively). Conclusions and Relevance The findings of this cross-sectional study revealed that after COVID-19 restrictions were lifted in Hong Kong, myopia prevalence among children was higher than before the pandemic, and lifestyle did not return to pre–COVID-19 levels. Younger children and those from low-income families were at a higher risk of myopia development during the pandemic, suggesting that collective efforts for myopia control should be advocated for these groups.
Succinate metabolism and its regulation of host-microbe interactions
Authors: Yi-han Wei, Xi Ma, Jiang-chao Zhao, Xiu-qi Wang, Chun-qi Gao
Journal: Gut Microbes (2023)

Succinate is a circulating metabolite, and the relationship between abnormal changes in the physiological concentration of succinate and inflammatory diseases caused by the overreaction of certain immune cells has become a research focus. Recent investigations have shown that succinate produced by the gut microbiota has the potential to regulate host homeostasis and treat diseases such as inflammation. Gut microbes are important for maintaining intestinal homeostasis. Microbial metabolites serve as nutrients in energy metabolism, and act as signal molecules that stimulate host cell and organ function and affect the structural balance between symbiotic gut microorganisms. This review focuses on succinate as a metabolite of both host cells and gut microbes and its involvement in regulating the gut – immune tissue axis by activating intestinal mucosal cells, including macrophages, dendritic cells, and intestinal epithelial cells. We also examined its role as the mediator of microbiota – host crosstalk and its potential function in regulating intestinal microbiota homeostasis. This review explores feasible ways to moderate succinate levels and provides new insights into succinate as a potential target for microbial therapeutics for humans.
Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers
Authors: Lucy M Carter, Zoe Wigston, Philip Laws, Edward M Vital
Journal: British Journal of Dermatology (2023)

Abstract Background Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response. Objectives We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers. Methods We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months. Results Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3–15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P &amp;lt; 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P &amp;lt; 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes. Conclusions These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.
Gut microbial metabolite butyrate improves anticancer therapy by regulating intracellular calcium homeostasis
Authors: Yibin Che, Guoyu Chen, Qianqian Guo, Yourong Duan, Haizhong Feng, Qiang Xia
Journal: Hepatology (2023)

Gut microbiota are recognized to be important for anticancer therapy, yet the underlying mechanism is not clear. Here, through the analysis of clinical samples, we identify the mechanism by which the gut microbial metabolite butyrate inhibits HCC and then explore new strategies for HCC treatment.In our study, we demonstrate that gut microbial metabolite butyrate improves anticancer therapy efficacy by regulating intracellular calcium homeostasis. Using liquid chromatography-mass spectrometry analysis, we found that butyrate metabolism is activated in HCC patients compared with healthy individuals. Butyrate levels are lower in the plasma of HCC patients by gas chromatography-mass spectrometry (GC-MS) analysis. Butyrate supplementation or depletion of short-chain Acyl-CoA dehydrogenase (SCAD) gene (ACADS), encoding a key enzyme for butyrate metabolism, significantly inhibits HCC proliferation and metastasis. The profiling analysis of genes upregulated by butyrate supplementation or ACADS knockdown reveals that calcium signaling pathway is activated, leading to dysregulation of intracellular calcium homeostasis and production of reactive oxygen species. Butyrate supplementation improves the therapy efficacy of a tyrosine kinase inhibitor sorafenib. On the basis of these findings, we developed butyrate and sorafenib coencapsulated mPEG-PLGA-PLL nanoparticles coated with anti-GPC3 antibody (BS@PEAL-GPC3) to prolong the retention time of drugs and enhance drug targeting, leading to high anticancer efficacy. BS@PEAL-GPC3 nanoparticles significantly reduce HCC progression. In addition, BS@PEAL-GPC3 nanoparticles display excellent HCC targeting with excellent safety.In conclusion, our findings provide new insight into the mechanism by which the gut microbial metabolites inhibit HCC progression, suggesting a translatable therapeutics approach to enhance the clinical targeted therapeutic efficacy.
KRAS Hijacks the miRNA Regulatory Pathway in Cancer
Authors: Angelina S. Bortoletto, Ronald J. Parchem
Journal: Cancer Research (2023)

Abstract Extensive studies have focused on the misregulation of individual miRNAs in cancer. More recently, mutations in the miRNA biogenesis and processing machinery have been implicated in several malignancies. Such mutations can lead to global miRNA misregulation, which may promote many of the well-known hallmarks of cancer. Interestingly, recent evidence also suggests that oncogenic Kristen rat sarcoma viral oncogene homolog (KRAS) mutations act in part by modulating the activity of members of the miRNA regulatory pathway. Here, we highlight the vital role mutations in the miRNA core machinery play in promoting malignant transformation. Furthermore, we discuss how mutant KRAS can simultaneously impact multiple steps of miRNA processing and function to promote tumorigenesis. Although the ability of KRAS to hijack the miRNA regulatory pathway adds a layer of complexity to its oncogenic nature, it also provides a potential therapeutic avenue that has yet to be exploited in the clinic. Moreover, concurrent targeting of mutant KRAS and members of the miRNA core machinery represents a potential strategy for treating cancer.
Acute hepatic failure in trimethoprim-induced drug rash with eosinophilia and systemic symptoms (DRESS)
Authors: Aveen Connolly, Sarah Walsh, Marianna Philippidou, Jon Salisbury, Daniel Creamer
Journal: British Journal of Dermatology (2023)

In this paper, we describe four cases of drug rash with eosinophilia and systemic symptoms (DRESS) caused by trimethoprim administered for the treatment of acne. All cases were complicated by acute hepatic failure.
Assessing the performance of ChatGPT in answering questions regarding cirrhosis and hepatocellular carcinoma
Authors: Yee Hui Yeo, Jamil S. Samaan, Wee Han Ng, Peng-Sheng Ting, Hirsh Trivedi, Aarshi Vipani, Walid Ayoub, Ju Dong Yang, Omer Liran, Brennan Spiegel, Alexander Kuo
Journal: Clinical and Molecular Hepatology (2023)

Background/Aims: Patients with cirrhosis and hepatocellular carcinoma (HCC) require extensive and personalized care to improve outcomes. ChatGPT (Generative Pre-trained Transformer), a large language model, holds the potential to provide professional yet patient-friendly support. We aimed to examine the accuracy and reproducibility of ChatGPT in answering questions regarding knowledge, management, and emotional support for cirrhosis and HCC.Methods: ChatGPT’s responses to 164 questions were independently graded by two transplant hepatologists and resolved by a third reviewer. The performance of ChatGPT was also assessed using two published questionnaires and 26 questions formulated from the quality measures of cirrhosis management. Finally, its emotional support capacity was tested.Results: We showed that ChatGPT regurgitated extensive knowledge of cirrhosis (79.1% correct) and HCC (74.0% correct), but only small proportions (47.3% in cirrhosis, 41.1% in HCC) were labeled as comprehensive. The performance was better in basic knowledge, lifestyle, and treatment than in the domains of diagnosis and preventive medicine. For the quality measures, the model answered 76.9% of questions correctly but failed to specify decision-making cut-offs and treatment durations. ChatGPT lacked knowledge of regional guidelines variations, such as HCC screening criteria. However, it provided practical and multifaceted advice to patients and caregivers regarding the next steps and adjusting to a new diagnosis.Conclusions: We analyzed the areas of robustness and limitations of ChatGPT’s responses on the management of cirrhosis and HCC and relevant emotional support. ChatGPT may have a role as an adjunct informational tool for patients and physicians to improve outcomes.
Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US
Authors: Joshua A. Jacobs, Daniel K. Addo, Alexander R. Zheutlin, Catherine G. Derington, Utibe R. Essien, Ann Marie Navar, Inmaculada Hernandez, Donald M. Lloyd-Jones, Jordan B. King, Shreya Rao, Jennifer S. Herrick, Adam P. Bress, Ambarish Pandey
Journal: JAMA Cardiology (2023)

The burden of atherosclerotic cardiovascular disease (ASCVD) in the US is higher among Black and Hispanic vs White adults. Inclusion of race in guidance for statin indication may lead to decreased disparities in statin use.
Association of Patients’ Direct Addition of Buprenorphine to Urine Drug Test Specimens With Clinical Factors in Opioid Use Disorder
Authors: Jarratt D. Pytell, Penn Whitley, Steven D. Passik, William L. Bundy, Eric Dawson, Brendan Saloner
Journal: JAMA Psychiatry (2023)

The direct addition of buprenorphine to urine drug test specimens to mimic results suggestive of adherence is a clinically significant result, yet little is known about the phenomenon.
High Nucleotide Diversity Accompanies Differential DNA Methylation in Naturally Diverging Populations
Authors: James Ord, Toni I Gossmann, Irene Adrian-Kalchhauser
Journal: Molecular Biology and Evolution (2023)

Abstract Epigenetic mechanisms such as DNA methylation (DNAme) are thought to comprise an invaluable adaptive toolkit in the early stages of local adaptation, especially when genetic diversity is constrained. However, the link between genetic diversity and DNAme has been scarcely examined in natural populations, despite its potential to shed light on the evolutionary forces acting on methylation state. Here, we analyzed reduced-representation bisulfite sequencing and whole-genome pool-seq data from marine and freshwater stickleback populations to examine the relationship between DNAme variation (between- and within-population) and nucleotide diversity in the context of freshwater adaptation. We find that sites that are differentially methylated between populations have higher underlying standing genetic variation, with diversity higher among sites that gained methylation in freshwater than those that lost it. Strikingly, although nucleotide diversity is generally lower in the freshwater population as expected from a population bottleneck, this is not the case for sites that lost methylation, which instead have elevated nucleotide diversity in freshwater compared with marine. Subsequently, we show that nucleotide diversity is higher among sites with ancestrally variable methylation and also positively correlates with the sensitivity to environmentally induced methylation change. The results suggest that as selection on the control of methylation state becomes relaxed, so too does selection against mutations at the sites themselves. Increased epigenetic variance in a population is therefore likely to precede genetic diversification.